EP0771546B1 - Method for detection of blood flow and/or intra- and/or extracorporal flowing liquid in a biological tissue - Google Patents

Description

The invention relates to an evaluation method for detecting the Blood flow and / or intra- and / or extracorporeally flowing Liquids in human, animal or biological Tissue.

A method with the features mentioned at the outset is known from the US 4,590,948 and is used to measure the Surface circulation. This is done from the fabric emerging photons in two areas, the are arranged equidistant from the entry area. The frequency and the intensity of the photons is detected by means of detectors. A depth-selective determination of the concentration of glucose is not possible with this known device.

DE 43 14 835 A1 discloses a device and a Method for determining the concentration of glucose in a biological matrix. There are at least two Detection measurements are provided, in each of which light as Primary light is radiated into the biological matrix propagated in the biological matrix along a light path, and a light intensity emerging as secondary light is measured. An evaluation is also provided at the from the intensity measurement values of the detection measurement by means of an evaluation algorithm and a calibration Glucose concentration is derived. This one too A method is not depth-selective flow detection possible.

From EP 0 728 440 A2, which has not been previously published, there are a Evaluation method and a device for depth-selective, known non-invasive detection of muscle activity, wherein photons from a coherent, monochromatic light source enters the tissue through a first area, the at different distances from this first area photons emerging from the tissue with respect to frequency and Number or intensity detected and from the information Frequency and / or number or intensity and / or exit location of the photons emerging again by means of a Evaluation program and / or algorithm depth-selective Conclusions about the strength of muscle activity and / or Number of active muscles and / or spatial location of the active ones Muscle in the tissue gains.

• Diagnose von Hauterkrankungen, z. B. Sclerodermia, Psoriasis
• Lokalisierung von Arterieskleroseerscheinungen
• Hilfestellung bei der Erkennung diabetischer Mikroangiophatie
• Beobachtung der arteriellen Vasomotion
• Überwachung der Sympathikusfunktionen in der Regionalanästhesie
• Durchblutungskontrolle bei Transplantationen, etc.

The skin as a border organ between humans and the environment fulfills a variety of functions. It serves to fulfill regulatory and immunological tasks and, last but not least, as a sensory organ. The skin is roughly composed of the epidermis and the underlying layer, the corium consisting of nerves, muscles and capillaries. The interaction of these muscles, nerves and capillaries regulates the microcirculation and controls all other tasks that are the responsibility of the skin. A determination and control of the blood flow to the skin can now serve to determine fluctuations or disorders thereof and to support a medical diagnosis. Below is just an extract of the various application examples:

• Diagnosis of skin diseases, e.g. B. Sclerodermia, psoriasis
• Localization of arterial sclerosis symptoms
• Assistance in the detection of diabetic microangiophathy
• Observation of arterial vasomotion
• Monitoring of sympathetic functions in regional anesthesia
• Blood flow control during transplants, etc.

Laser Doppler systems have been used for decades Skin vascular diagnostics used. The biggest limitation of the conventional laser Doppler systems are based on their low effective depth of penetration and analysis "direction-independent" signals. This reduces the Use on measuring the microcirculation of the skin, being a measuring volume the size of a hemisphere with a Diameter of max. 1 mm can be examined. Moreover deliver the devices that have been used in clinical practice for skin circulation from methodical and metrological reasons no comparable Readings. The users of these conventional systems, e.g. B. Flowmeters have moved on to this, mainly that Time behavior of the measurement signals after defined stimulations to assess the microcirculation.

The invention is therefore based on the object Evaluation methods for the detection of blood flow and / or intra- and / or extracorporeal fluids in biological tissue.

The evaluation method according to the invention is essentially characterized in that the surface areas in arranged at different distances from the first region are and one from detected interference patterns or Frequency beats in connection with the respective Area as the exit point of the exiting Photons using an evaluation program or algorithm depth selective information of the relative change of the Flow rate or flow rate and spatial location of the Blood flow and / or intra- and extracorporeally flowing Liquids in the tissue gain.

This evaluation method uses the property of Interaction of electromagnetic waves on tissue and Blood and / or fluid components. Because of a sufficiently small wavelength and the associated adequate ratio of wavelength to geometric Dimension of the body or tissue to be detected, is suitable the spectral range from visible to infrared electromagnetic waves. At the same time sufficient detection depth in biological tissue is reached. This procedure is non-invasive and the one from the Interactions that arise are proportional to Speed, number and depth of each yourself moving blood and / or fluid components, so that from this information clearly, especially a relative one Change in flow rate or the like is detectable and assignable is. Investigations both in everyday clinical practice and in special, medical, pharmacological or industrial questions on depth-selective detection blood flow and / or intra- and / or extracorporeal Flowing liquids can be used with this device or this evaluation method extremely simple, painless and perform reproducibly.

The invention is based i. w. then, using laser light o. Like., coherent and monochromatic electromagnetic Radiation on the skin surface or tissue surface of the to investigate. The photons penetrate the tissue and are according to the optical parameters of the tissue scattered or absorbed. Since the spread with a Change in the direction of propagation of the photons goes hand in hand, photons are also remitted from the tissue, i.e. to the Scatter the surface of the tissue or skin and kick again from the tissue. This remission from the tissue emerging photons has a decreasing intensity with increasing distance from the point of entry of the photons. Another feature of the biological tissue is that Light is not uniform, i.e. isotropic, in all directions is scattered, but a forward characteristic at Scattering process is maintained. That is expressed in the so-called anisotropy factor g for scattering processes, which at Tissue assumes a value g of approximately 0.9. A value of g = 0 would isotropic, a value g = 1 correspond to pure forward scatter.

Using a simple model is explained below to what extent a detection of the remitted Photons a conclusion on the condition of the tissue or Blood flow and / or intra- and / or extracorporeally flowing Liquids are possible: Consider e.g. Photons that about 5 mm from the point of incidence of the photons from the tissue step out again, then with a high probability can be assumed that these emerging again Photons through different scattering processes in about one semicircular or similar trajectory through the tissue have moved. Due to the special implementation of the However, the evaluation procedure is certain that the start of the Path curve at the entry point of the photons and the end of the Trajectory lies at the measuring point of the emerging photons. Provided these photons emerging again provide any information with respect to the movement of the blood flow and / or intra- and / or should have extracorporeal fluids in any case, it can be assumed that the right next to the The point of irradiation again only exits the tissue from the tissue Information regarding just below the surface flow through layers of tissue, while those in further away from the point of radiation emerging photons Provide information also about deeper layers of tissue can. This model observation thus shows that through detection of photons emerging from the tissue selectively with increasing distance from the irradiation site Information can be obtained from certain tissue depths can.

It is known to measure moving, scattering particles the optical Doppler effect is used. Thereby light experiences in the scattering process a frequency shift that is proportional to the speed of the moving particle increases. Under Taking the Doppler effect into account, e.g. in superficial tissue layers of blood flow in the tissue be determined. For an optimal Doppler signal of the Blood flow and / or intra- and / or extracorporeally flowing Preserving fluids in deeper tissue layers is a light wavelength of the light source, in particular the Lasers, which are only slightly absorbed by the tissue becomes. There are therefore wavelengths in the range of approximately 600 nm to about 1200 nm, preferably at about 820 nm.

Every now and then it is discussed in the literature that coherent laser light when irradiated by the tissue Variety of scattering processes its coherence properties could lose. By interferometric examinations However, it has been shown that a certain proportion of photons that emerge from the tissue at a greater distance from the radiation site, can interfere with the incident photon beam, from what undoubtedly it must be concluded that the coherence characteristics of these scattered photons are still present. So it is but also possible at larger distances from the detectors the Doppler signals with the corresponding one Frequency shift of the emerging frequency-shifted photons in / from different depths detect. The photons mix with the Doppler shift Frequency with such photons that have no Doppler shift have experienced, i.e. only from a rigid or immobile matrix were scattered. At the detection site at the The tissue surface thus creates an intensity beat between frequency-shifted and non-frequency-shifted Photons. This leads to a local speckle pattern, the Intensity varies with the Doppler frequency and thus from an optical detector can be measured.

In principle, the signals are evaluated in the form that two detectors, preferably at continuous intervals The irradiation phase is symmetrical to the irradiation location record remitted photons. The output signals of this Detectors are evaluated and processed accordingly to the desired information or statements regarding blood flow and / or intra- and / or extracorporeal flowing fluids.

Anisotropiefaktor, Streukoeffizient, Absorptionskoeffizient, mittlere freie Weglänge.

In summary, it can be stated that such an evaluation method can be carried out particularly in the area of the "therapeutic window", that is to say at wavelengths in the range from 600 nm to 1200 nm, in which the scattering of the incident photons is not negligible. The optical absorption from the scattering of light in human tissue can be described in more detail by the photon transport theory. The path of a photon scattered into the skin is followed. The photon either experiences elastic scattering at the individual local scatterers or is completely absorbed. From this, the penetration depth and the scattering process can be determined for laser light in the red wavelength range (600 nm) or the infrared wavelength range (1200 nm). Although the so-called mean free path is relatively short, light of this wavelength range can penetrate deep into the tissue, since the scattering mainly takes place in the forward direction (so-called Mie scattering), the scattering processes are much more frequent than the absorption and absorption in the tissue for it Wavelength range is small compared to other wavelengths. The propagation of light in tissue is described according to the transport theory by the following parameters:

Anisotropy factor, scattering coefficient, absorption coefficient, mean free path.

An overall view of the theoretical as well as performed experimental studies indicate that with the inventive ring-shaped interference structures available in a concentric position with regard to the irradiation location are. With increasing lateral distance from the point of incidence most likely place the photons in the tissue larger ways back and accordingly penetrate deeper the tissue. To the contained in the photon state Information about movements of the illuminated tissue To be able to evaluate, the light source should be specific Properties such as having a sufficient coherence length, be monochromatic and operable in single mode.

An important prerequisite for obtaining the desired one Information is a sufficiently high coherence length so that an interference pattern can be achieved. The emergence of the Interference pattern is due to the assumption that Photons scattered near the tissue or skin surface are not experiencing any frequency changes, these so to speak non-frequency shifted photons with such Photons that are at depth on moving particles, i.e. on the moving blood and / or fluid components are scattered and thereby experience a change in frequency, interfere. Therefore, if the frequency-shifted scattered light which was scattered on moving particles with quasi original light not shifted in frequency, on the If the detector surface is covered, a Beat frequency or an interference pattern. Around To get beat frequencies from deeper tissue layers is the use of a wavelength in the range from 600 nm to approx. 1200 nm is required, also on a sufficient coherence length of the light source must be observed should. It could be shown that typical Interference patterns are also detectable for large tissue depths and that the information with increasing distance of the Detector area comes from increasing depth of tissue.

This verification is also for large lateral distances Detector area from the irradiation location in a range of up to approx. 15 mm has been successfully carried out. Indeed lateral distances of up to 30 mm also appear in practice to be possible in principle.

A particularly advantageous embodiment of the entrance described evaluation method according to the invention in having a light source with a long coherence length, especially larger than 10 cm, and used again emerging photons at a certain distance of the first area, in particular at least two at the same time closely adjacent or symmetrical to the first area arranged surface areas, detected. Through this Measure becomes the prerequisite for a particularly good one Signal / noise ratio created.

It has proven to be advantageous that the detected signals under two surface areas other leads a differential amplifier function and possibly an adaptive filter function and possibly a frequency and / or Subjects cepstrum analysis. Through this type of procedural signal evaluation can be an accurate analysis of muscle activity are preserved.

Further advantages and possible uses of the present Invention result from the following description of the Exemplary embodiments with reference to the drawings.

Figur 1

eine schematische Ansicht eines ersten Ausführungsbeispiels der erfindungsgemäßen, auf ein Gewebe aufgesetzten Vorrichtung in Seitenansicht,

Figur 2

ein zweites Ausführungsbeispiel der erfindungsgemäßen Vorrichtung in Seiten- und Unteransicht,

Figur 3

ein drittes Ausführungsbeispiel der erfindungsgemäßen Vorrichtung in schematischer Darstellung,

Figur 4

ein Blockdiagramm einer adaptiven Filterfunktion und

Figur 5

ein Blockschaltbild einer Cepstrumanalysefunktion.

Show it:

Figure 1

2 shows a schematic view of a first embodiment of the device according to the invention, placed on a fabric, in a side view,

Figure 2

a second embodiment of the device according to the invention in side and bottom view,

Figure 3

a third embodiment of the device according to the invention in a schematic representation,

Figure 4

a block diagram of an adaptive filter function and

Figure 5

a block diagram of a cepstrum analysis function.

The device 10 shown in Figures 1 and 2 for depth-selective detection of blood flow and / or intra and / or extracorporeal fluids in human, animal or the like tissue 12 has a Light source 14, in particular a semiconductor laser, for Emission of photons into tissue 12 or Blood vessels on. The device 10 is with a carrier plate placed on the tissue 12 or the skin 18 of the tissue, photons passing through a first region 16, which locally i. w. is well defined, in the tissue 12 or the blood vessels enter. The photons are in the tissue 12 or Blood vessels partly scattered, partly absorbed, whereby some possible photon paths 66, 68 figuratively and are shown schematically in Figure 1. It is clearly visible that the photons continue to increase with increasing penetration depth 64 removed from the first area 16 from the tissue 12 again escape.

Furthermore, the device 10 has a plurality of detectors 20 Detection of the areas 18 of the skin 18 or of the tissue 12 emerging photons. The others Surface areas 22 are at different distances from that first area 16 spaced.

The light source 14 is according to the embodiment of the figure 1 an attachable to the face of the fabric 12 Optical fiber piece 24 assigned. From the embodiment of Figure 2 it can be seen that instead of Leichtleitfaserstücks 24 also a collimation optics 26 for Focusing the laser light on the tissue 12 or the skin 18 can be used.

The detectors 20 each have a face 12 of the tissue 12 attachable optical fiber 28, to which a photodiode 30 o. Like. is subordinate.

The light source 14 is a polarization filter after and Detectors 20 upstream. Furthermore, between the Optical fiber 28 and the photodiode 30, optionally absorption filter 34 introduced.

The wavelength of the semiconductor laser is in the range of approximately 600 nm to about 1200 nm, preferably at about 820 nm.

As in particular from the exemplary embodiment in FIG. 2 can be seen, the further surface areas 22 and assigned detectors 20 adjacent to each other in pairs and i. w. arranged in a row in a row 38, each Pair 36 has a different distance from the first region 16 and the distances between adjacent pairs 36 in any case in Embodiment are equidistant. It is understood that other distances of the individual detectors 20 with respect to the first area 16 can be selected, this is measured based on the special requirements of the respective system and based on the specialist knowledge of the average specialist. The others Surface areas 22 and the corresponding detectors 20 are up to a maximum distance 56 of about 15 to 30 mm from the first region 16 arranged.

As can be seen in particular from FIG. 3, those of paired surface areas 22 or from the corresponding Detectors 20 detected two signals 42, 44 each of the two Inputs of a differential amplifier 46 supplied. This Measure advantageously also takes advantage of the Embodiments of Figures 1 and 2 application, then corresponding pairs 36 of detectors to one Differential amplifier 46 are connected. The signals of the Detectors 20 become, among other things, an adaptive one Filter function 52 and a cepstrum analysis function 78 subjected (Figure 5).

The entire device with the exception of a processor 54, that is the light source 14, the detectors 20 and the electronic ones Components, such as preamplifier 48, differential amplifier 46 and analog / digital converter 50 are together in one measuring head 58 housed the flat on the tissue 12 or the skin 18 can be placed. The measuring head 58 thus has only one Connection by means of an electrical conductor to the evaluation unit, especially processor 54. The inside of the measuring head is filled with a filling compound 62.

In deviation from the arrangement of the detectors 20 of the Embodiments of Figures 1 and 2 shows the embodiment according to FIG. 3 further surface areas 22 or assigned Detectors 20 which i. w. on one through the first area 16 straight lines 40 and in pairs symmetrical on both sides of the first region 16 are arranged.

The adaptive filter function 52 in FIG. 4 has two channels 70, 72, with the first channel 70 the unchanged Input signal leads, but in channel 72 Delay stage 74 is switched on. By means of the Adaptation stage 76, the filter coefficients as long changed until the difference between the unfiltered Input signal of channel 70 and the filtered signal of the Channel 72, becomes minimal on average.

According to Figure 5, which is a block diagram of the Cepstrum analysis function 78 represents the signals as Time-amplitude function is shown graphically and with a real-valued Fast Hartley transformation (FHT) or one Fast Fourier Transform (FFT) or another Frequency analysis algorithm in a power spectrum 88 or Power spectrum disassembled. Here, the in the Beat frequencies contained sub-frequencies regarding analyzed their intensity and range. The Service spectrum 88 is in real time with a base number greater than 64 points determined and graphically for each A / D converter channel 82 processed into a kind of "waterfall display". This range of services is used for both a moment analysis subjected to the intensity as well as for the frequency. The so The moments created can be combined into a vector and display them graphically. Overall, there is Cepstrum analysis function 78 from the series connection a filter function 80, an A / D converter 82, one discrete time window 84, a Fast Fourier transform 86, a power spectrum 88, a logarithmic function 90, an inverse Fast Fourier transform 92, one Lifter function 94, a Fast Fourier transform 96 and finally the modified range of services 89. This one the latter process is also called cepstrum analysis function 78 referred to, causing characteristic, changing Frequencies can be made visible. The meaning of Cepstrum analysis function is particularly that spectra subjected to a precise analysis with periodic fluctuations can be. The cepstrum becomes the phaseless Range of services formed.

All measurement data, evaluations and analyzes can be on one graphical user interface visualized and archived for further processing on mass storage devices. The different signals of the individual channels can also continuing with a cross-correlation, the autocorrelation and other signal evaluation algorithms compared and be evaluated.

The embodiment of Figures 1 and 2 works i. w. how follows. A semiconductor laser arranged in the measuring head 58 emits coherent, monochromatic light, especially one Coherence length greater than 10 cm, directly into the Optical fiber piece 24 a. The light is in that Optical fiber piece 24 to the surface of the skin 18 in the first Area 16 forwarded. The optical fiber piece 24 should preferably a mono-mode fiber with a minimum diameter 300 µm to the light output of the semiconductor laser to be able to transfer. Depending on the version, the Optical fiber piece 24 are dispensed with when the laser light with the aid of collimation optics 26 directly on the Skin surface is focused. The remitted light turns on the optical fibers 28 in the further surface areas 22 recorded and forwarded to the photodiodes 30. Before or behind the optical fibers 28 and / or before Optical fiber piece 24 each have absorption filters 34 and Polarization filter 32.

All fibers and filters are preferred in one opaque plastic or ceramic frame on the Measuring head 58 locked. The fibers are off-center in pairs a longitudinal axis 100 on a carrier plate of the measuring head 58 arranged. The distance between the individual pairs 36 is same, this distance in different versions can be designed variably. The optical fibers 28 should do not exceed a diameter of 400 µm, because that Signal / noise ratio with decreasing diameter getting better. However, as it grows smaller Diameter the intensity of the measurement signal from, so that here Compromise is to be found. When choosing the photodiodes 30 is preferably to make sure that the individual photocurrents at same illumination differ only minimally. The complete evaluation electronics consisting of preamplifier 48 and Differential amplifier 46 is in the shielded housing of the Measuring head 58 integrated. Also the analog / digital converter 50 can be arranged in the measuring head 58. However, there is also the possibility of these components outside the measuring head 58 to be placed on a measurement card so that only digitized Signals are passed to the processor 54. The The purpose of evaluation electronics is that of the photodiodes 30 converting and amplifying the coming current into a voltage, what is done by means of the preamplifier 48. Then it is arranged and switched in pairs Photodiodes 30 by means of the differential amplifier 46 a Signal difference formed and further amplified. Finally is each differential amplifier 46 with an analog / digital converter 50 12 to 16 bit resolution and a minimum sampling rate of approx 20 kHz downstream. Thus, each pair becomes 36 of the photodiodes assigned an A / D converter channel. The digitized signals are sent to processor 54 for evaluation.

It remains to be mentioned that in contrast to the execution of Figures 1 and 2 in the embodiment of Figure 3 die Pairs 36 of the photodiodes 30 and the surface areas 22 are not are arranged in pairs next to each other, but so to speak diametrically and symmetrically left and right of the first area 16 are formed. With this arrangement, too by forming the difference between the output signals corresponding pairs 36 of photodiodes 30 improved signal / noise ratios form. However, this arrangement, especially in the presence of a preferred direction of the Light propagation in the tissue can be somewhat disadvantageous.

In this respect, it is the represented Embodiments of Figures 1 and 2 with respect to the pair Arrangement of the photodiodes 30 or further surface areas 22 a preferred embodiment of the invention.

LIST OF REFERENCE NUMBERS

10 -

contraption

12 -

tissue

14 -

light source

16 -

first area

18 -

skin

20 -

detector

22 -

area

24 -

optical fiber guide

26 -

collimating optics

28 -

optical fiber

30 -

photodiode

32 -

Polariationsfilter

34 -

absorption filter

36 -

Pair

38 -

line

40 -

Just

42 -

signal

44 -

signal

46 -

differential amplifier

48 -

preamplifier

50 -

A / D converter

52 -

filter function

54 -

processor

56 -

distance

58 -

measuring head

60 -

ladder

62 -

filling compound

64 -

penetration depth

66 -

photon path

68 -

photon path

70 -

channel

72 -

channel

74 -

delay stage

76 -

adaptation stage

78 -

cepstrum analysis

80 -

filter function

82 -

A / D converter

84 -

Time window

86 -

Fast Fourier Transformation

88 -

range of services

90 -

Logarithmierfunktion

92 -

inverse fast fourier transform

94 -

Lifterfunktion

96 -

Fast Fourier Transformation

98 -

mod. range of services

100 -

longitudinal axis

Claims (3)

1. Evaluating method for detection of blood flow and/or intracorporally and/or extracorporally flowing liquids in human, animal or biological tissue (12), wherein photons of a coherent monochromatic light source (14) are allowed to enter the tissue (12) through a first region (16) and photons exiting the tissue again are detected in spaced surface regions (22) with respect to frequency and number or intensity, characterised in that the surface regions (22) are arranged at different spacings from the first region (16) and depth-selective data concerning the relative change in throughflow quantity or throughflow speed and physical position of the blood flow and/or intracorporally and/or extracorporally flowing liquids in the tissue (12) are obtained by means of an evaluating program or evaluating algorithm from detected interference patterns or frequency fluctuations in conjunction with the respective surface region (22) as exit location of the photons exiting again.
2. Evaluating method according to claim 1, characterised in that a light source (14) with a large coherence length, in particular greater than 10 cm, is used and the photons exiting again in each instance at a specific spacing from the first region (16) are detected, in particular isochronously, in two surface regions (22) which are closely adjacent or arranged symmetrically relative to the first region (16).
3. Evaluating method according to claim 2, characterised in that the detected signals in each instance of two surface regions (22) are fed inter alia to a differential amplifier function (46) as well as subjected optionally to an adaptive filter function (52) and optionally to a frequency and/or cepstrum analysis function (78).

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